Questions on the dynamics of enzyme function can, in most cases, only be answered byactivity measurements. However, if activities of a complex biological sample are assayedusing classical biochemical approaches, single enzymatic components can not be resolved.Hence, activity based protein profiling seeks to functionally characterise all individual componentsof a targeted enzyme class within a complex sample. This is achieved by smallmolecule probes, which exclusively detect enzymes in their active state.Recently developed ABPP methods achieve functional characterisation of serine hydrolasesin living cells and intact tissue, using copper mediated alkyne azide [2+3] Huisgencycloaddition for reporter coupling [Speers et al., 2003] [Schicher et al., 2009].The current study sets out to improve the performance of the CuAAC-ABPP methodreported by Schicher et al. and to develop an activity based imaging approach.In the course of the work described herein,the feasibility of an activity based imagingapproach was shown for several over expressed lipases. However, when applied to adipocytemodel cells, the method did not achieve visualisation of endogenous esterases/lipases. Resultsobtained from gel based experiments imply that the kinetics and side reactions ofCuAAC and Staudinger ligation do not offer sufficient sensitivity for the detection of lowabundant probe-enzyme complexes. Hence, the data presented herein lay the ground forfurther developments of ABPP and activity based imaging approaches using ?clickable? esterase/lipase probes.