This commentary considers modulation as a factor of potential biological importance in assessment of risk of radiofrequency (RF) energy emitted by communications systems and other technologies. Modulation introduces a spread of frequencies into a carrier waveform, but in nearly all cases this spread is small compared to the frequency of the carrier. Consequently, any nonthermal (field-dependent) biological effects related to modulation must result from interaction mechanisms that are fast enough to produce a response at radiofrequencies. Despite considerable speculation, no such mechanisms have been established. While a variety of modulation-dependent biological effects of RF energy have been reported, few such effects have been independently confirmed. Some widely discussed effects, for example a reported modulation-dependent effect of RF fields on the efflux of calcium from brain tissue, remain controversial with no established biological significance. The lack of understanding of the mechanisms underlying such effects prevents any assessment of their significance for communications signals with complex modulation characteristics. Future research should be directed at confirmation and mechanistic understanding of reported biological effects related to modulation. While modulation should be considered in the design of risk studies involving communications-type signals, it should not compromise other aspects of good study design, such as maintaining adequate statistical power and identifying dose-response relationships.