Two dimensional atomic crystals, like grapheme (G) and molybdenum disulfide (MoS 2 ), exhibit great interest in electronic and optoelectronic applications. The excellent physical properties, such as transparency, semiconductivity, and flexibility, make them compatible with current organic electronics. Here, we review recent progress in the understanding of the interfaces of van der Waals (vdW) heterostructures between small organic molecules (pentacene, copper phthalocyanine (CuPc), perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA), and dioctylbenzothienobenzothiophene (C 8 -BTBT)) and layered substrates (G, MoS 2 and hexagonal boron nitride (h-BN)). The influences of the underlying layered substrates on the molecular arrangement, electronic and vibrational properties will be addressed.