Second harmonic generation (SHG) is a nonlinear optical imaging technique that provides high-resolution images of intact tissues and cellular structures without the need for exogenous labels. SHG occurs in media lacking a center of symmetry, such as anisotropic crystals or interfaces, and is particularly effective for imaging highly ordered structural proteins and biological membranes. Collagen, a major component of connective tissues, exhibits significant SHG due to its noncentrosymmetric helical structure. SHG is generated primarily in the dermis of skin, not in the epidermis or subcutaneous fat. SHG has advantages such as high spatial resolution, minimal surface reflection, and the ability to separate excitation and detection signals. It is also useful for studying collagen orientation in tissues. SHG is an instantaneous process, and its signal intensity depends on the square of the molecular surface density. Unlike two-photon fluorescence, SHG does not arise from an absorptive process but from nonlinear polarization induced by intense laser fields. SHG signals are generated in a small volume of tissue and have distinct spectral and temporal characteristics compared to two-photon fluorescence. SHG microscopy has been used to image living cells, endogenous structural proteins, and biomolecular arrays. It is also useful for studying various biochemical and biophysical processes, including collagen nanostructure, spatial orientation of fibrous structures, and structural changes in collagen gels. SHG has potential for clinical applications, such as quantifying disease status, monitoring extracellular matrix restructuring, and visualizing skin lesions. Nonlinear methods like SHG require minimal labeling, but new markers like ZnO nanoparticles can be useful. SHG is often used in combination with other techniques like multiphoton fluorescence and CARS for multimodal imaging. CARS is a third-order nonlinear process that uses four-wave mixing to generate a signal, and it offers advantages such as direct signal generation, narrow bandwidth, and no influence of autofluorescence. CARS has been used for imaging lipid vesicles, fat droplets, and organelles in living cells. It is non-destructive and allows for real-time diagnosis of diseases like breast cancer. CARS has potential for ex vivo and in vivo studies, and it can provide high-resolution images of tissues. A micro-endoscope allows for minimally invasive imaging of cellular processes in the spinal cord. The probing depth of nonlinear microscopy is limited by tissue scattering, but tissue optical clearing can increase this depth. Terahertz spectroscopy and imaging, which operate in the intermediate frequency range between infrared and microwave, have potential applications in biology and medicine due to their ability to detect biomolecular vibrations and penetrate tissues with minimal scattering.Second harmonic generation (SHG) is a nonlinear optical imaging technique that provides high-resolution images of intact tissues and cellular structures without the need for exogenous labels. SHG occurs in media lacking a center of symmetry, such as anisotropic crystals or interfaces, and is particularly effective for imaging highly ordered structural proteins and biological membranes. Collagen, a major component of connective tissues, exhibits significant SHG due to its noncentrosymmetric helical structure. SHG is generated primarily in the dermis of skin, not in the epidermis or subcutaneous fat. SHG has advantages such as high spatial resolution, minimal surface reflection, and the ability to separate excitation and detection signals. It is also useful for studying collagen orientation in tissues. SHG is an instantaneous process, and its signal intensity depends on the square of the molecular surface density. Unlike two-photon fluorescence, SHG does not arise from an absorptive process but from nonlinear polarization induced by intense laser fields. SHG signals are generated in a small volume of tissue and have distinct spectral and temporal characteristics compared to two-photon fluorescence. SHG microscopy has been used to image living cells, endogenous structural proteins, and biomolecular arrays. It is also useful for studying various biochemical and biophysical processes, including collagen nanostructure, spatial orientation of fibrous structures, and structural changes in collagen gels. SHG has potential for clinical applications, such as quantifying disease status, monitoring extracellular matrix restructuring, and visualizing skin lesions. Nonlinear methods like SHG require minimal labeling, but new markers like ZnO nanoparticles can be useful. SHG is often used in combination with other techniques like multiphoton fluorescence and CARS for multimodal imaging. CARS is a third-order nonlinear process that uses four-wave mixing to generate a signal, and it offers advantages such as direct signal generation, narrow bandwidth, and no influence of autofluorescence. CARS has been used for imaging lipid vesicles, fat droplets, and organelles in living cells. It is non-destructive and allows for real-time diagnosis of diseases like breast cancer. CARS has potential for ex vivo and in vivo studies, and it can provide high-resolution images of tissues. A micro-endoscope allows for minimally invasive imaging of cellular processes in the spinal cord. The probing depth of nonlinear microscopy is limited by tissue scattering, but tissue optical clearing can increase this depth. Terahertz spectroscopy and imaging, which operate in the intermediate frequency range between infrared and microwave, have potential applications in biology and medicine due to their ability to detect biomolecular vibrations and penetrate tissues with minimal scattering.