Tattooing is an ancient practice that enjoys continued popularity. Although a modern, professionally performed tattoo is generally safe, complications can occur. A skin biopsy of all tattoo reactions is recommended as some tattoo reactions have systemic implications. Tattoo-related infections are seen days to decades after tattooing, and range from acute pyogenic infections to cutaneous tuberculosis. In particular, non-tuberculous mycobacterial infections happen in tattoos with increasing frequency and are introduced at the time of tattooing through contaminated ink or water used to dilute inks. Despite a transition in tattoo pigments from metal salts to industrial azo dyes, hypersensitivity reactions also persist, and include eczematous, granulomatous, lichenoid, and pseudoepitheliomatous patterns (among others). Granulomatous tattoo reactions can be a clue to cutaneous or systemic sarcoidosis, particularly in the setting of interferon use. Pseudoepitheliomatous tattoo reactions have substantial overlap with squamous cell carcinoma and keratoacanthoma, making diagnosis and management difficult. Other malignancies and their benign mimics can occur in tattoos, raising questions about the safety of tattoo ink and its role in carcinogenesis.