INTRODUCTION: The disorder insomnia represents a relevant and frequent condition in clinical care. Cognitive behavioral therapy of insomnia (CBT-I) is regarded as first line treatment. Pharmacotherapy can be considered if CBT-I is not available or effective. Therefore, pharmacological approaches for disturbed sleep are still among the most widely prescribed pharmacological treatments in clinical care. AREAS COVERED: In this review, the authors highlight basic physiological pathways of sleep regulation to understand fundamental pharmacological principles of sleep medicine. Available guidelines and reviews are summarized and recommendations formulated regarding the use of benzodiazepines and hypnotic benzodiazepine receptor agonists, melatonin and melatonin receptor agonists, sedating antidepressants, antipsychotics and antihistamines, and orexin receptor antagonists in insomnia disorder. Variations in the treatment of insomnia disorder in subpopulations with increased prevalence of sleep disorders - childhood, pregnancy and old age - are specified. EXPERT OPINION: The well-established off-label use of hypnotic drugs should evocate a debate about a better alignment of clinical practice and scientific evidence and guidelines. Better understanding of sleep regulation could help in the development of completely new substance classes. Focusing subjective sleep disturbances, such as superficial sleep perception might help identify novel pathways.