Ketamine is an NMDAR antagonist that has been widely used for clinical anesthesia. In addition, low-dose ketamine has analgesic, anti-inflammatory and antidepressant effects, which have attracted extensive attention in recent years. However, how low-dose ketamine can affect the higher cognitive functions remain unclear. Here we review the effects of low-dose ketamine on working memory (WM). WM is the ability to temporally hold and manipulate information in the brain. It mainly relies on a network involving several key brain areas such as the prefrontal cortex (PFC), hippocampus, etc. WM plays a key role in many complex cognitive processes, thus to understand how it may be affected by low-dose ketamine is informative and important for its clinic use. Here we review the studies showing that acute or chronic use of low-dose ketamine will impair working memory in a sophisticated way. The possible mechanisms underlying such impairments include breaking the excitation/inhibition (E/I) balance in the PFC, changing the short-term and long-term synaptic plasticity, activating the DA pathway, etc. We also pointed out that to fully reveal the effects of low-dose ketamine on WM and related neural mechanism, future multi-facet studies combining behavioral tests, electrophysiology, neuroimaging, histology, etc, and with more comparable dosage and time of medication would be needed. We hope that this review will be instrumental for facilitating appropriate use of low-dose ketamine in clinical settings.