Before introducing a new chemical or product into the market, we use a multistep process to assess contact sensitization risk for the product and key ingredients. The risk assessment process is a comparative toxicological approach in which data on the inherent toxicity of a material and the exposure to it (through manufacturing or consumer use or foreseeable misuse) are integrated and compared with data generated on benchmark materials of similar chemistry or product application, or both. The steps included in the risk assessment process include: (1) analytical characterization and literature review for skin sensitization data, (2) preclinical skin sensitization testing (murine local lymph node assay and/or Buehler guinea pig test), (3) human repeat insult patch testing (HRIPT), (4) clinical use testing, and (5) monitoring and follow-up of consumer comments. Our decision-tree approach to skin sensitization risk assessment is a dynamic process that incorporates numerous risk assessment points. The results obtained with the new material are compared with prior results with benchmark materials and then further evaluated relative to the type of exposure expected in the workplace and under normal use (and product misuse) conditions. This review summarizes each step of the contact sensitization risk assessment process and provides some specific examples to illustrate the value of the approach.