The routine use of Computer-Assisted Surgery (CAS) in a wide range of surgical procedures and specialties is being hindered by the lack of suitable user interface for surgical environments. While many computer techniques and software exist to assist surgeons in their tasks, the inability of these tools to fit into existing surgical setups and procedures (both physically and practically) significantly reduces their efficiency and limits their deployment. There are two major drawbacks to existing user interfaces for CAS: (1) they consist mostly of poor adaptations of the existing desktop computer keyboard and mouse interaction paradigm, and (2) they are designed to function just like desktop applications, where the software is the focus of attention of the user, therefore adding to the per-operative workload of the surgeon. I propose a new approach to user interfaces for CAS by introducing M/ORIS, a Medical/ Operating Room Interaction System. M/ORIS is an intelligent collection of sensors and logic modules that are designed to specifically address the need for suitable user interaction in the operating room (OR). M/ORIS provides two layers of interaction that address the fundamental limitations of existing surgical user interfaces: (1) a set of new interaction modalities that are compatible with surgical constraints (i.e. sterile and non-obstructing) and (2) a new interaction paradigm, based on these new modalities, that automates some interaction tasks in order to reduce the interruptions to the surgical process currently required to interact with the computer in the OR. This work describes a detailed analysis of Human-Computer Interaction methods for CAS, and proposes a new approach to Surgeon-Computer Interaction. The design of the new interaction paradigm, as well as the implementation of its building modules, are presented, including a new method to perform real-time, visual detection and tracking of obstructed body parts in indoors environments and a mechanism to perform surgical activity monitoring. The performance of each component of M/ORIS and the behavior of the whole system are then analyzed, and considerations for future improvements are given.