Background: Surgical site infections following Neurosurgical procedures are often associated with significant morbidity and mortality; constitute added economic burden and affect the patient’s quality of life negatively. The primary source of pathogenic microorganisms is the patient’s skin flora, making preoperative skin antisepsis a primary focus for preventive strategies. Objective: To review literature on various antiseptic agents used in neurosurgical practice and find out the most appropriate and effective agent(s) in preventing surgical site infections. Methods: A search in PubMed and Google scholar was made and various published articles on the use of antiseptic agents in preventing SSI in neurosurgery were reviewed. Results: Reviewed literature revealed that sequential use of 4% chlorhexidine and 10% povidone iodine is associated with significant reduction in both transient and resident’s pathogens, as well as surgical site infections. Conclusion: A review of relevant scientific literature supports sequential use of 4% chlorhexidine and 10% povidone iodine in prevention of surgical site infections in neurosurgery