This chapter is a summary of key issues and solutions related to nonlinear regression–fitting nonlinear models to data. The details of diverse issues are revealed in the book Nonlinear Regression Modeling for Engineering Applications: Modeling, Model Validation, and Enabling Design of Experiments by Rhinehart, R. R., John Wiley & Sons, Inc., Hoboken, NJ, 2016b. Here, they are summarized and presented with an optimization application perspective.