Panic disorder and agoraphobia are among the most frequent referrals in mental health care. The treatment of agoraphobia has received considerable attention from the early days of behavior therapy onward. As of the early 1980s, diagnostic and theoretical refinements led to an increased emphasis on the occurrence and treatment of panic attacks. The Diagnostic and Statistical Manuals of Mental Disorders, edited by the American Psychiatric Association, as well as cognitive models of psychopathology, are responsible for these developments. In the present chapter, effective cognitive-behavioral treatment protocols are described, based on these recent insights. After an overview of diagnostic considerations and assessment methods, the treatment of panic disorder is described in detail. Next, strategies in the reduction of agoraphobic avoidance are outlined. Even within the realm of cognitive-behavioral therapy, many treatment approaches have been suggested. In this chapter we focus on the most frequently used variants. Obstacles in the implementation and the conduct of treatment often occur and for that reason deserve ample discussion. Case illustrations and verbatim therapy interactions demonstrate the practical realization of the original treatment plans.