WHAT IS KNOWN AND OBJECTIVE: Psychotherapy has traditionally competed with psychopharmacology. As drugs have become the more dominant treatment in psychiatry and primary care, this approach is increasingly criticized as limited in scope, lacking in robust outcomes and too heavily influenced by the pharmaceutical industry. Our objective is to show that recent advances in neurobiology are clarifying that learning and environmental experiences, such as psychotherapy, change brain circuits as do drugs. The leading notion of how therapeutic effects occur in psychiatric disorders is that they happen when symptoms are reduced by improving the efficiency of information processing in hypothetically malfunctioning brain circuits. COMMENT: With this formulation of psychiatric symptoms and their relief, it is not surprising that both psychotherapy and psychopharmacology can be clinically effective for treating psychiatric disorders, or indeed that combining them can be therapeutically synergistic. Psychotherapy, including a new spinoff of cognitive behavioural therapy called trial-based therapy, like many other forms of learning, can hypothetically induce epigenetic changes in brain circuits that can enhance the efficiency of information processing in malfunctioning neurons to improve symptoms in psychiatric disorders, just like drugs. WHAT IS NEW AND CONCLUSION: Psychotherapies can be conceptualized as epigenetic 'drugs', or at least as therapeutic agents that act epigenetically in a manner similar or complementary to drugs. These findings are leading to a paradigm shift in psychiatry such that psychotherapy is experiencing a come-back as various standardized, brief, goal-directed psychotherapies are being integrated with drug treatment of psychiatric disorders by psychopharmacologists who have traditionally relied on a drugs-only approach.