The choice between lipid-mediated transfection and electroporation is largely dependent on the cell type and the characteristics of the nucleic acid being transfected. Some cell types, including many immortalized cell lines, can be readily transfected with transfection agents and methods developed for use with siRNA. Other cell types, such as some finite cell lines or freshly isolated primary cells, present more of a challenge. Electroporation, particularly with optimized buffers and protocols, can be a very successful means of siRNA delivery into these cells. In both cases, optimization of conditions is often required for efficient and reproducible siRNA delivery. This is best accomplished by using a positive control siRNA and then monitoring knockdown of a target at the mRNA level.