**Abstract**

The pineal hormone melatonin (MLT) is a derivative of the amino acid *L*-tryptophan and controls the circadian diurnal rhythm and the seasonal biorhythm. Exogenous administration is aimed at alleviating sleep-related dysfunctions and jet lag, as it decreases sleep-onset latency, increases total sleep time and improves overall sleep quality. Besides these indications, MLT has been shown to have other actions, such as antioxidant, immune enhancement and anticancer. It has also been shown to be useful against cardiovascular, neurological and psychiatric diseases. In the context of this work, a review of the related literature on the modified release of MLT from its *per os* administered formulations is presented, including the utilization of the design of experiments (DoE) for the selection of the optimal composition of melatonin formulations. The chapter offers an account of the recent advantages on MLT's solid dosage forms suitable for treating sleep disorders, referring either to its onset or maintenance.

**Keywords:** melatonin, circadian rhythm, sleep disorders, modified release, oral solid dosage forms, *per os* administration, experimental design
