Microscopic colitis (MC) is a common cause of chronic diarrhea. The 2 most frequent forms of MC are collagenous colitis and lymphocytic colitis. Over the past years, the incidence and prevalence of microscopic colitis are rising and this is largely attributed to a greater awareness, and concomitantly an increasing number of diagnoses. Patients with microscopic colitis report watery, nonbloody diarrhea of chronic course, abdominal pain, weight loss, and fatigue that may impair patient's health-related quality of life. The underlying mechanisms involved in the pathogenesis of microscopic colitis remain unspecified but is probably multifactorial. Collagenous colitis and lymphocytic colitis may represent specific mucosal responses to different luminal agents in predisposed individuals, resulting in an uncontrolled immune response. Genetic predisposition, altered modulation of cytokines and miRNAs, and aberrant response to drugs seem to be involved in the development of MC. Despite the progress of knowledge, still many questions remain unsolved regarding the etiology, pathophysiology, and optimal management of MC. This review gives an update on the immunological aspects of collagenous colitis and lymphocytic colitis.