Layered chalcogenides have important applications in a variety of low-dimensional functional materials and devices, including thermoelectrics and topological insulators. The highly anisotropic crystal structures, bonding, and mechanical properties in such materials give rise to complex dislocation behavior. Here, I present our work investigating the atomic- and nanometer-scale structures and arrangements of dislocations in layered chalcogenides, linking the observed defect configurations to the materials mechanics at the nanoscale. As one set of examples, I will discuss our atomic resolution electron microscopic observations of dislocations in Bi2Te3 and ZrTe5. These dislocations can exhibit complex, dissociated cores that result from the relief of strain associated the large Burgers vectors in these systems. I will also discuss the structure of line defects at interfaces in chalcogenides. One key example is the mediation of misfit strain and crystal growth by interfacial disconnections during the growth of Sb2Te3 precipitates.