Human pigmentation involves production and dispersion of melanin by epidermal melanocytes to neighboring keratinocytes. Melanin synthesis or melanogenesis occurs within the specialized organelle termed melanosomes where the amino acid L-tyrosine serves as the starting precursor. Melanocytes from individuals of different pigmentary phenotypes differ in their rate and types of melanin synthesis, as well as in the rate and manner of melanosome transfer. Modern molecular biology methods and the use of transgenic animals have greatly advanced our understanding in the molecular and cellular mechanisms regulating human pigmentation and its disorders. This review examines recent advances in the regulation of human pigmentation and their implication in treatments for the pigmentary disorders.