With the introduction of new technologies, surgical procedures have been varying from free access in open surgery towards limited access in minimal invasive surgery. During such procedures, surgeons have to manoeuver the instruments from outside the patient while looking at the monitor. Long and slender instruments are developed that can insert into the patients body through small incision(s) or natural orifice(s) with help of an endoscope following instrument created or transluminal pathways. In these types of procedures, called pathway surgery throughout this thesis, the incisions limit the instrumentmotion and reduce the number of degree of freedom (DoF) from six to four, while the curvature of the pathway restricts the instrument motion within a narrow tunnel, further reducing the number of DoF down to two. After the establishment of conventional instruments, steerable instruments (instruments with one steerable segment on its tip) and manoeuvrable instruments (instruments with multiple steerable segments) are under development, yet the development of an intuitive and effective control interface for such instruments remains a challenge. The goal of this thesis is to assess the manoeuvrability of currently available commercial steerable instruments, and to find potential solutions to manoeuvring difficulties of medical instruments used in pathway surgery. To achieve this goal, we developed a simulator emulating the shaft and handle of a manoeuvrable instrument, and we conducted experiments that investigate the effects of various factors of manual manoeuvrability on human performance in a simulated surgical pathway task. As many studies have reported new developments of steerable and manoeuvrable instruments, the first part of this thesis includes a survey of literature related with manual control methods for handheld steerable instruments, to investigate what would be the bestsuited manual control method for future instruments for pathway surgery. A full overview of manoeuvrable approaches and their controls interfacing were provided, and a novel way of categorizing control methods for handheld manoeuvrable instruments based on physical coupling between the controllers was proposed. This study shows that in the case of controlling single steerable segment, direct- as well as indirect- control methods have been developed, whereas in the case of controlling multiple steerable segments, a gradual shift can be noticed from parallel and serial control to integrated control. The survey results are linked to future developments in pathway surgery, that is, instead of providing full manoeuvrability at each steerable segment, Integrated Single-Segment control (ISS, i.e. using one controller to manoeuvre the leading segment while the other steerable segments copy the leading motion) would generate a user experience similar to conventional steerable instruments in aspects like eye-hand coordination, 3-dimensional vision and surgical workflow. The second part of this thesis provides two experiments that compare control methods for steerable instruments used in neuroendovascular surgery and laparoscopic surgery respectively. Firstly, an experiment was designed to investigate the effectiveness of two widely used 1DoF control methods, rotating control and sliding control, and their effects on human performance, such as accuracy, safety and intuitiveness. Based on directions of the control motions, four handles were built. The slider-vertical handle provided general faster and safer performance, whereas rotator handles were more preferred by participants at the end of the experiment. Subsequently, two 2DoF steerable instruments, one controlled by the thumb and the other by the wrist, were compared in a positioning task in a portable laparoscopic trainer. The experiment results showed that although the two compared control methods were not significantly different in terms of time, thumb control was strongly preferred by novices. Currently the development of manoeuvrable instruments is still in its infancy, the ISS concept and the other outcome from the literature review was a trigger to develop a simulator, Endo-PaC (EndoPathController), allowing great possibility of investigating manual manoeuvrability for manoeuvrable medical instruments. Endo-PaC mimics the shaft and handle of a manoeuvrable instrument with standard dimensions, measures the control motion in 5DoF, and is electronically connected to a laptop computer. Custom-designed software visualizes circular tunnels, and participants were asked to guide the virtual steerable tip without collision towards a target that located at the end of the virtual curved tunnel as fast as possible. The last part of this thesis presents four experiments using Endo-PaC for assessing two main aspects of manual controllability, cognitive aspect and ergonomic aspect, respectively. The first two experiments investigated two factors, visual-display compatibility and local disorientation, both of which contribute to spatial disorientation and yield a high cognitive load for surgeons in an endoscopic navigation task. The latter experiments assessed two methods of control mode, DR (Deflection Rotation) control and DD (Double Deflection) control, and two methods of control device, joystick control and handgrip control, for their effect on human performance with regard to task time, path length tracelled by the virtual tip, motion smoothness, subjective workload as well as personal preference. It is concluded that manual controllability is key to the success ratio of using handheld instruments in minimally invasive surgery. To new MIS procedures, such as pathway surgery, manoeuvrable instruments featuring ISS control allows less manoeuvrability but provide a strong benefit leading to easy control and high precision by just one clinician. Experiments with novice participants revealed that, in order to improve the manual controllability for ISS control during a navigation task, control interfacing featuring DD control leads to faster and safer performance compared with DR control, while handgrip control appeared to be more intuitive to master than joystick control. Furthermore, eliminating the visual-display misalignment, so that the controlled tip movements are in line with the surgeons hand movements, and providing a visible cue, so that the surgeon knows where the instruments heading for in the next advancing step, could greatly reduce the training time, facilitate performance and cause less cognitive load.