Chemical reactions leading to imaging of poly(2-hydroxyethyl methacrylate) (PHEMA) based materials are investigated. Positive imaging is obtained upon exposure to deep UV and electron beam radiation following a chain scission mechanism. The presence of the OH group adds the possibility of development in alkaline aqueous solutions with considerably higher sensitivities than in the case of PMMA. On the other hand, negative tone lithography can be achieved with the addition of photo-acid generators that induce crosslinking, arising mainly from transesterification reactions. Reaction mechanisms have been investigated mostly by MS studies supported by FTIR and UV spectroscopies. Micropatterning characteristics for deep UV and electron beam radiation have also been evaluated. Submicron patterning capabilities are demonstrated for both positive and negative imaging although higher resolution is hindered by strong swelling phenomena during development. Nevertheless, specific patterning applications including novel schemes for use in biomaterials and microsystems are anticipated.