The scanning probe microscope (SPM) system is emerging as an increasingly important tool for non-intrusive interrogation of biomolecular systems in vitro. Its particular merit is that it retains complete functionality in a biocompatible fluid environment and can track the dynamics of cellular and molecular processes in real time and real space at nm resolution, as an imaging tool, and with pN force-sensing/imposing resolution, as an interaction tool. The capability may have relevance as a test bed for monitoring cellular response to environmental stimuli and pharmaceutical intervention. We shall also review the better-known recent contributions of SPM towards explanatory and predictive descriptions of biomolecular interactions at surfaces and interfaces, and describe some recent attempts to reconfigure the SPM platform for demonstration of novel bio-device applications.