Background: Lumbosacral radicular pain, commonly known as sciatica, is a prevalent and challenging condition arising from nerve root compression in the lumbar spine due to various underlying pathologies. Epidural steroid injections (ESIs) are often employed for symptomatic relief when conservative treatments fail. While ESIs are minimally invasive and provide localized pain relief, their safety, especially concerning neurological complications, remains a critical concern. Objective: This article reviews the neurological complications associated with ESIs and compares the safety and effectiveness of various corticosteroid formulations administered via transforaminal, interlaminar, or caudal injection techniques. Method: A comprehensive literature search was conducted using PubMed, Scopus, and the Cochrane Library, focusing on studies published within the last ten years. Inclusion criteria encompassed studies addressing lumbosacral radicular pain, the safety and efficacy of ESIs with different corticosteroid formulations, and comparative effectiveness analyses of injection routes. Data on corticosteroid types, formulation characteristics, adverse effects, efficacy measures, and patient demographics were extracted and analyzed both qualitatively and quantitatively. Results: Findings indicate significant variation in safety profiles and effectiveness among different corticosteroid formulations used in ESIs. Dexamethasone, often favored for its efficacy, has been linked to potential neurological complications, particularly concerning preservatives like benzyl alcohol. Comparative studies suggest that while dexamethasone may provide adequate pain relief, it may lead to higher rates of repeat injections compared to particulate steroids like triamcinolone. Conclusion: The review underscores the need for a personalized approach to ESI administration, balancing the benefits of pain relief against potential long-term complications. The data highlights a pressing need for ongoing research into optimizing corticosteroid use and ensuring patient safety in the management of lumbosacral radicular pain.