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Café-au-lait spots are a usual kind of skin disease characterized by epidermal pigmentation. They are mainly treated by lasers, which include Q-switched Nd:YAG laser, Q-switched ruby laser, etc. However, the efficacy of single use of these lasers is far from satisfactory, and the treatment of Café-au-lait spots remains troublesome due to high recurrence, injury to surrounding skin and instability of responses. With further insight into the pathogenesis and histopathology of café-au-lait spots, several treatment strategies have been developed to target the pathogenesis and histopathological changes in order to achieve better outcomes.