STM has become a powerful surface tool not only for imaging evolving surface structures and morphologies but through them for determining quantitative values of surface energetics and stress. In this review, using the growth of pure Ge on Si(001) as a model system, we have presented a comprehensive picture of the effect of misfit strain on thermodynamic properties that become the driving forces for morphologies and other properties that influence the early stages of heteroepitaxy. The strain relaxation proceeds in steps via different relaxation modes. The analysis process and methods discussed here should be generally applicable to similar problems in a much wider range of systems. On Ge-covered Si(001), strain relaxation begins with the formation of ordered dimer vacancies. The form and magnitude of the dimer vacancy-vacancy interaction can be determined by measuring and analyzing the vacancy distribution functions. The formation of vacancy lines changes the step energies and morphologies, reversing the relative roughness of two types of monatomic steps on Si(001). The response of surface morphology, for surfaces covered with different amounts of Ge, to an external uniaxial stress reveals an intriguing interplay of surface stress, structure, and stoichiometry. As strain increases with increasing film thickness, other modes of stress relief become important. In particular, a transition from 2D layers to 3D clusters, the classic transition predicted by Stranski and von Krastanov, must occur. This transition turns out to be very complex, beginning with a breakup of the 2D layers into smaller sections of 2D layer and a subsequent formation of coherent metastable 3D crystallites and only much later ending with relaxed larger-sized clusters as expected from the Stranki-Krastanov theory. The discovery, by STM, of this special kind of {105}-faceted coherent Ge island on Si(001) has provided new insights to the conventional Stranski-Krastanov theory. These microscopic "hut" islands also show great promises for future technological applications as quantum dot devices. Formation of defects (vacancies, steps, etc.) and formation of coherent 3D islands are two typical strain-induced surface roughening processes. However, strain relaxation can have much richer manifestations. The form and process of surface roughening, i.e., the mode of strain relaxation, depend strongly on growth conditions (deposition rate, temperature, substrate miscut and orientation, alloy concentration, etc.) and can be affected by externally applied stress.23,93 For example, on a vicinal surface, the bunching of steps created by miscut is the dominant relaxation mechanism during the growth of SiGe alloy on Si(001).94,95 It has been shown95 that there exists a generic step bunching instability of a strained vicinal surface, arising from the long-range elastic step-step attraction induced by lattice mismatch.95 Such step bunching also leads to self-organization of step bunch arrays that are potentially useful for growing quantum wires.96 While surface roughening, in general, prevents the growth of smooth films, it can be useful for fabricating nanostructures.90 A good control of roughening processes through the manipulation of growth kinetics and surface thermodynamics, leading to self-organization of superlattices of quantum dots and quantum wires, has become an attractive route to nanofabrication.