In this chapter, we will give an intuitive introduction to the general problem of 3D medical image segmentation. We will give an overview of the popular and relevant methods that may be applicable, with a discussion about their advantages and limits. Specifically, we will discuss the issue of incorporating prior knowledge into the segmentation of anatomic structures and describe in detail the concept and issues of knowledge-based segmentation. Typical sample applications will accompany the discussions throughout this chapter. We hope this will help an application developer to improve insights in the understanding and application of various computer vision approaches to solve real-world problems of medical image segmentation.