Extrapyramidal side effects of psychotropic medicines are usually experienced by patients in the first few weeks of initiating therapy. Patients stabilized on these medications who present with distressing complaints akin to akathisia may be triggered by other factors. This report presents two cases of drug-drug-induced akathisia. Case A is a patient with schizophrenia who was being managed with risperidone 2 mg tablet daily for the past 3 years. She fell ill and reported to a nearby clinic where she was prescribed ciprofloxacin and artemether/lumefantrine tablets for the treatment of an infection and malaria. She presented 7 days later to her psychiatrist with complaints of restlessness, tremor, palpitations, insomnia, and resurgence of obsessive thoughts. Case B is a patient who was diagnosed with first-episode psychotic depression and admitted for 10 days. Her medications on admission were fluphenazine decanoate 25 mg depot injection once, olanzapine 10 mg tablet daily, and fluoxetine 20 mg capsule daily. On discharge, ciprofloxacin 500 mg tablet every 12 hours for 5 days and fluconazole 150 mg capsule once were added to her medications for the treatment of a urinary tract infection. She reported back to the hospital a day after discharge with complaints of restlessness, "seizures," tremor, abdominal discomfort, and weight gain. Both patients were diagnosed with akathisia using ICD-10 classification and the Barnes akathisia rating scale and managed with anticholinergics, benzodiazepines, and beta blockers. Other measures employed in managing the akathisia included reducing the dose of the antipsychotic and/or switching antipsychotics. Despite these management measures, the symptoms of akathisia persisted and only resolved after 4weeks. Upon the resolution of symptoms, Case A continued treatment on olanzapine 5 mg tablet daily and fluoxetine 20 mg capsule daily while Case B continued treatment on risperidone 2 mg tablet daily and fluoxetine 20 mg capsule daily. Using Naranjo's adverse drug reaction causality assessment scale, Medscape drug interaction checker, and literature review, a possible and probable case of drug-drug-induced akathisia was made for Case A and Case B. This report is to create more awareness about psychotropic-antimicrobial-induced akathisia. The information underpins the need for health professionals to consider adverse drug-drug interactions as the probable cause of extrapyramidal side effects experienced by patients on antipsychotics.