The skin is the largest organ of the human body and plays a major role in maintaining homeostasis and protection. As the main component of skin, collagen has a key role in providing integrity and elasticity to this organ. Several factors, including autoimmune disease, aging, and stress, can change the quantity and integrity of skin collagen. These factors impair collagen quality and consequently affect skin function. Stress seems to affect the integrity of skin collagen through glucocorticoid-mediated processes that alter its synthesis and degradation. Glucocorticoids also affect skin quality through modulation of the immune system. This review will briefly present comprehensive data from both animal and human studies delineating processes that modulate alterations in collagen in general, and will treat in more detail the consequences of stress on skin collagen.