This study aims to explore the comparative efficacy and acceptability of psychotherapies, pharmacotherapies, and their combinations for insomnia. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, CINAHL, and ClinicalTrials.gov were searched for randomized clinical trials (RCTs) examining the comparative efficacy in which a psychotherapy and a pharmacotherapy for insomnia were directly compared with each other, or in which a combination of psychotherapy and pharmacotherapy was compared with either alone. The analysis included data from 23 RCTs. In 18 of 23 studies, cognitive behavior therapy for insomnia (CBT-I) was the psychotherapy. At post-treatment, CBT-I showed higher subjective sleep efficiency (SE), and lower subjective wake time after sleep onset (WASO) and insomnia severity index (ISI) score. Compared with CBT-I plus pharmacotherapy, pharmacotherapy showed lower subjective SE, and higher subjective sleep latency (SL), PSG measured SL, subjective WASO, and ISI score. Overall, the findings derived from post-treatment data suggested that CBT-I is more beneficial in treating insomnia compared with pharmacotherapy. CBT-I combined with pharmacotherapy is beneficial in improving some sleep parameters (i.e., subjective SE, SL, WASO, and PSG measured SL) compared with pharmacotherapy alone. Daily clinical decisions should consider these findings on the relative efficacy of the principal approaches to insomnia treatment.