Over the last several decades, plasmonic nanoparticles, in particular those of gold have been extensively employed in biological investigations due to their unique optical and physical properties as well as their safe use in the biological environment. In this review, the utility of gold nanoparticles to probe intracellular environments and reveal dynamic measurements in real-time at the single-cell level is described. The fundamental principles and their associated methodologies behind their unique interaction with light and the associated methodologies are discussed. Gold nanoparticle synthesis and functionalization with organelle-targeting ligands is also highlighted. The review ends with an outlook on the challenges and efforts that need to be taken in order to fully realize the potential of utilizing gold nanoparticles in the real-time molecular mapping of single cells. (C) 2015 Elsevier Ltd. All rights reserved.