Internet-based cognitive behavior therapy (ICBT) is a promising treatment that may increase availability of cognitive behavior therapy (CBT) for psychiatric disorders and other clinical problems. The main objective of this study was to determine the applications, clinical efficacy and cost-effectiveness of ICBT. The authors conducted a systematic review to identify randomized controlled trials investigating CBT delivered via the internet for adult patient populations. Searches to identify studies investigating cost-effectiveness of ICBT were also conducted. Evidence status for each clinical application was determined using the American Psychologist Association criteria for empirically supported treatments. Of 1104 studies reviewed, 108 met criteria for inclusion, of which 103 reported on clinical efficacy and eight on cost-effectiveness. Results showed that ICBT has been tested for 25 different clinical disorders, whereas most randomized controlled trials have been aimed at depression, anxiety disorders and chronic pain. Internet-based treatments for depression, social phobia and panic disorder were classified as well-established, that is, meeting the highest level of criteria for evidence. Effect sizes were large in the treatment of depression, anxiety disorders, severe health anxiety, irritable bowel syndrome, female sexual dysfunction, eating disorders, cannabis use and pathological gambling. For other clinical problems, effect sizes were small to moderate. Comparison to conventional CBT showed that ICBT produces equivalent effects. Cost-effectiveness data were relatively scarce but suggested that ICBT has more than 50% probability of being cost effective compared with no treatment or to conventional CBT when willingness to pay for an additional improvement is zero. Although ICBT is a promising treatment option for several disorders, it can only be regarded as a well-established treatment for depression, panic disorder and social phobia. It seems that ICBT is as effective as conventional CBT for respective clinical disorder, that is, if conventional CBT works then ICBT works. The large effects and the limited therapist time required suggest that the treatment is highly cost effective for well-established indications.