Sleep spindles are key electroencephalogram (EEG) oscillatory events that occur during non-rapid eye movement (NREM) sleep. Deficits in sleep spindles are present in populations with sleep and neurological disorders, and in severe mental illness. Pharmacological manipulation of these waveforms is of growing interest with therapeutic potential in targeting spindle deficits relating to memory impairment. This review integrates studies that provide insight into the feasibility of manipulating sleep spindles by using psychoactive drug classes, with consequent effects on sleep-dependent memory. Most studies showed that benzodiazepines and Z-drugs consistently enhanced sleep spindle activity unlike other psychoactive drug classes reviewed. However, how these spindle enhancements translate into improved sleep-dependent memory remains to be fully elucidated. From the few studies that examined both spindles and memory, preliminary evidence suggests that zolpidem may have some therapeutic potential to enhance declarative memory through boosting sleep spindle activity. There is a greater need to standardise methodological approaches for identifying and quantifying spindle activity as well as more exploratory studies to elucidate the role of spindle enhancement for other types of memory.