The strength of in situ electron microscopy lies in its ability to observe directly material changes which are pertinent to bulk processes. The most rigorous experiments employ a purpose-built specimen holder to simulate specific testing conditions (e.g. heating, cooling, straining, environment), with the associated microstructural changes deduced from appropriate micrographs, diffraction patterns or video-recordings. The influence of the electron microscope itself must always be taken into account (e.g. thin-foil specimen, large electron flux, high electron energy). However when artifacts are overcome, remarkable insight into the mechanisms of the behavior of solids can be achieved. The purpose of this article is to review our work in extending this capability into the high-resolution regime, so that atomic reactions can be followed. In the right circumstances this allows straightforward interpretation of atomic-scale phenomena.Our studies have employed a Philips EM430ST, 300 kV transmission electron microscope (TEM) with about 0.2 nm resolution. To-date we have carried out only heating experiments, utilizing the standard side-entry, single-tilt specimen holder (model number PW 6592), mainly on reactions at semiconductor interfaces. The zone axis orientation necessary for high-resolution TEM is obtained by careful sectioning of the substrate crystals and judicious positioning in the heating holder. The imaging conditions (including drift) can be optimized at a temperature slightly below that required for the changes of interest, so that recording can be initiated immediately on ramping up.