The high prevalence of depression globally and the severe burden of this life-threatening mental illness necessitate an evidence-based approach to its treatment, in order to offer best-possible relief to those suffering from it. The present bestpractice guideline was originally developed by a team of psychiatrists, psychologists, and other mental health professionals at a large psychiatric teaching hospital and outpatient clinic network in Michigan, USA. The document draws from several current major guidelines for the treatment of adult patients with depressive disorders published by national and international health organisations, such as the American Psychiatric Association (USA), Canadian Network for Mood and Anxiety Treatments (Canada), National Institute for Health and Care Excellence (UK) and World Health Organization (EU). The present document emphasizes the areas of broad consensus across these guidelines and, as such, the treatment recommendations contained herein represent the current “gold standard” in the field of psychiatry in the West. Part I of this two-part series covers a range of relevant psychiatric treatment aspects, from general patient management to treatment-stagespecific and population-specific recommendations. Special attention is given to pharmacotherapy, somatic therapies, treatment strategies for non-response and management of perinatal depression. Additional resources, including clinicianand patient-oriented websites and links to the full-text major published guidelines, where available, are provided. Psychiatric clinicians are encouraged to utilise the evidence-based practice recommendations for best-possible patient outcomes.