Harmonic nanoparticles were first introduced in 2006 as biomarkers for nonlinear imaging. This review provides a general explanation of the physical mechanism at the basis of this novel approach, highlighting its benefits and the complementarity to fluorescent/luminescent labels. A series of application examples from the very recent literature are reported, ranging from in vitro cell monitoring to the first proofs of in vivo imaging and rare event detection in physiological fluids.