This chapter will present the computational approach of registering images from different modalities based on manual selection of matching pairs of landmarks. Here we will present an image registration workflow based on MATLAB’s image processing toolbox using the identification of sites of clathrin-mediated endocytosis by correlative light electron microscopy (CLEM) as an example. In the Appendix section, we will discuss the concept of image transformations and how to generate them based on pairs of landmarks. We will also learn how to fit a 2D Gaussian for a more accurate positioning of the landmarks.