Melanophores or melanocytes, originated from the neural crest cells, contain melanosomes which are membrane-bound vesicles. Melanosomes are filled with dark coloured pigment called melanin, which has a crucial function in the biological color adaptation of vertebrates. Melanophore control via melanosome trafficking with microfilaments produce a variety of striking color pattern. Melanosome relaxation and contraction during pigment transfer is similar to the relaxation and contraction of smooth muscle cells. Studies have revealed that melanophores of all vertebrates including fish, amphibians, reptiles, mammals are functionally modified smooth muscle cells. The present chapter highlights the experimental based studies that have shown the comparison of melanophores with smooth muscle cells.