This review paper presents: (i) an overview of the present state of knowledge of the human NADPH oxidases and their clinical relevance; (ii) the authors’ own published analysis of the properties and biological significance of the only NADPH oxidase of Saccharomyces cerevisiae, Yno1; and (iii) the function of both Yno1 and Nox4 in the regulation of the actin cytoskeleton, which may be important for the mobility of cancer cells, as studied in a neuroblastoma cell line. This evidence concerns the gene NOX4 and cancer.