Several powerful new techniques can examine gene function in mammals. Recombinase systems and kidney-specific promoters enable gene knockout and overexpression. Genetic systems induced on administration or removal of antibiotics or hormones permit control of gene expression. Gene silencing using short interfering RNA expression systems should accelerate loss-of-function studies. Thorough characterization of animals that have undergone conditional gene targeting has already provided insights into renal development and diseases. Here we discuss the advantages and pitfalls of currently available gene-targeting systems.