Heteronuclear coherence transfer in liquid-state NMR applications has been traditionally performed using pulse-interrupted delay schemes such as INEPT-type pulse trains. So far, the alternative use of heteronuclear cross-polarization (HCP) has only been limited to a few cases involving exclusively in-phase to in-phase transfers. In this revision work a theoretical description on the effect and the characteristic anisotropic features of HCP is introduced in terms of product operator formalism. A very intuitive and simple graphical black-box approach based on a pictorial non-classical vector representation that only consider the available input/output magnetization is also presented to understand the general transformations that are undergoing under such rather complex HCP processes. The appropriate manipulation of magnetization components during the HCP block offers novel concepts in pulse sequence design. In this way, new liquid-state multidimensional NMR methods incorporating HCP-driven processes have recently been developed and successfully applied for both small-to-medium-sized molecules and large labeled bio-molecules, as will be discussed in this review. © 2007 Bentham Science Publishers Ltd.