Molecular imaging with TOF-SIMS is considered with respect to existing technical challenges and potential applications. The major goal is to improve the sensitivity of measurement since desorption of molecules occurs from an area of much less than 1 mum in diameter and the number of molecules is limited. Improved knowledge of the fundamental aspects of the molecular collision cascade, bombardment with focused beams of cluster ions, laser postionization of neutral molecules and ion correlation techniques are suggested as areas where there may be considerable payoff. Potential applications to biomaterials, single biological cells, rapid screening in genomics and proteomics and molecular electronics are considered. (C) 2002 Elsevier Science B.V. All rights reserved.