OBJECTIVES: Biologics play a crucial role in managing some of the rheumatological disease, thus it is important for clinicians, healthcare institutions and policy-makers to understand why biologics are initiated or refused so as to make better decisions in the course of improving patients’ disease outcomes. Although there were many studies investigating factors associated with initiation of biologics for patients with rheumatological conditions, there have been no systematic review that provide a comprehensive summary in this area. The objective of this paper is to provide a summary of factors associated with biologics initiation for patients with rheumatological conditions. METHODS: We performed a literature search in PubMed®, Embase® and PsycInfo®. We identified and screened studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Factors were presented according to patient, disease-related, therapy-related, healthcare team-related and system in-place factors. RESULTS: A total 1755 articles were being reviewed and 25 articles were found to be relevant to our objective. Forty eight factors reviewed were categorized into five main categories namely patient factors (n=13), disease-related factors (n=12), therapy-related factors (n=10), healthcare team related factors (n=4) and system in-place related factors (n=9). The factors studied by the published papers found to be associated with decisions to initiate biologics varies widely. An illustration for biologics initiation was also presented to allow clinicians to better understand the complex nature of decision making. CONCLUSIONS: Forty eight factors of five different categories were found to be associated with biologics initiation for patients with rheumatological conditions. Clinicians need to be mindful of the complex nature of these factors to optimize therapeutic outcomes of patients with rheumatological conditions. Healthcare intuitions and policies makers ought to be aware of any potential barriers to successful biologics treatment and address them accordingly.