In this review, we summarize a new line of experimentation showing that attentional orienting can bias information processing in the working memory domain as well as in the perceptual domain to optimize goal-directed behavior. A new experimental paradigm was developed, which revealed that spatial orienting cues that appear after perceptual events (retro-cues), when these have been internalized into working memory representations, can retrospectively enhance performance to a similar degree as spatial precues appearing before perceptual events. As part of their facilitatory action, retro-cues diminish the costs of retrieving items from increasing loads within working memory. Hemodynamic and electrophysiological brain imaging experiments show a high degree of overlap between brain areas and dynamics involved in spatial orienting in the working memory domain compared to the perceptual domain. In addition, functional magnetic resonance imaging points to the selective involvement of frontal areas during spatial orienting in the working memory domain. The roles of different frontal areas remain to be clarified but may include both early roles in guiding spatial shifts occurring within a mnemonic context as well as selection of memorized targets amidst distracting stimuli. Experiments have also begun to reveal the ability to orient attention selectively to object-based representations in working memory and suggest that the neural representations of objects in working memory can be directly modulated by this process. The findings bolster contemporary notions of a strong theoretical relationship between attentional orienting and working memory, suggesting that these two cognitive functions interact in more ways and directions than previously considered.