New insights into the origin of superstructure modulations in Bi-Sr-Ca-Cu-O superconductors with the idealized formulation Bi2Sr2CaCu2O8 (2212) have been obtained primarily from electron microscopy. Systematic investigations of the Bi-Sr-Ca-Cu-O samples annealed in both reducing and oxidizing environments show that the superconducting transition temperature (Tc) decreases for the oxygen-annealed samples containing oxygen interstitials. Electron diffraction has revealed significant local differences in the modulation periodicities depending on the annealing environment. Superstructure modulations have also been found in the samples prepared entirely in reducing nitrogen. Rare-earth doped Bi2Sr2Ca1−xYxOy have also been examined in different environments. High precision microanalysis using quantitative EDX shows that the modulations are insensitive to the concentration of cation point defects.Proposed models for superstructure modulations include: a rigid rotation of CuO5 polyhedra which may result from small differences in the equilibrium bond lengths between Bi-O and Cu-O layers; ordering of Bi-concentrated and deficient zones;