This review highlights the recent applications of non-linear optical (NLO) microscopy to study obesity-related health risks. A strong emphasis is given to the applications of coherent anti-Stokes Raman scattering (CARS) microscopy where multiple non-linear optical imaging modalities including CARS, sum-frequency generation (SFG), and two-photon fluorescence are employed simultaneously on a single microscope platform. Specific examples on applications of NLO microscopy to study lipid-droplet biology, obesity-cancer relationship, atherosclerosis, and lipidrich biological structures are discussed.