Aim: The aim of this article was to review experimental studies of laser irradiation of human and animal cells in culture to assess the photobiomodulatory effects of such irradiation. Background: Previous studies have shown that various types of cells respond differently to laser irradiation, depending on irradiation parameters. Cellular outcomes measured or examined include cell numbers, cell viability, and ultrastructural features. A review of these studies may provide a further insight into the clinical effects brought about by laser light on cells and tissues, including laser effects in wound healing and repair of nerves and skeletal muscle after injury. Methods: A systematic review was completed of original research articles investigating the effects of laser therapy on human and animal cells in culture (January 2002 to September 2009). Relevant articles were primarily sourced from PubMed and Medline by using EndNote X1, and from secondary searches. Search terms were “cell proliferation,” “laser therapy,” “laser irradiation,” “laser phototherapy,” and “phototherapy.” Results: In total, 46 relevant articles were included in the review, comprising work completed on a variety of cell types. Although results consistently demonstrated the potential of laser irradiation to affect cellular proliferation in a wavelength- and dosage-dependent manner, the relevance of other key irradiation parameters, such as irradiance, to such effects remained unclear. Conclusions: Findings from studies of cells in culture clearly demonstrate the ability of laser irradiation to modulate (typically stimulate) cellular proliferation. The relevance of some irradiation parameters remains occult and represents an important area for further research.