Recent advances in nanoparticle systems for improved drug delivery display a great potential for the administration of active molecules. Generally, the lipid systems presented the advantage of their low toxicity due to their composition of physiological lipids compared to polymeric particles. The physico-chemical stability of the lipid carriers showed variations due to their numerous compositions and structures. This review consequently focuses on the physico-chemical stability of dispersions in the nanometer range where the lipids are the main or the only components. It highlights on the destabilization mechanisms, the techniques used to detect this destabilization and the inductors of the destabilization. Finally, the methods used to optimize the stability of lipid nanoparticle systems are described in the last part.