Perianal fistulas are a common complication of Crohn's disease (CD) that has, historically, been challenging to manage. Despite the strong available evidence that anti-tumor necrosis factor (anti-TNF) agents are useful in the treatment of perianal fistulizing Crohn's disease (PFCD), a significant number of these patients do not respond to therapy. The use of therapeutic drug monitoring (TDM) in patients with CD receiving biologic agents has evolved and is currently positioned as an important tool to optimize and guide biologic treatment. Considering the treatment of PFCD can represent a challenge; identifying novel tools to improve the efficacy of current treatments is an important unmet need. Given its emerging role in other phenotypes of Crohn's disease, the use of TDM could also offer an opportunity to enhance the effectiveness of available therapies and improve outcomes in the subset of patients with PFCD receiving biologics. Overall, there is mounting evidence that higher anti-TNF drug levels are associated with better rates of "fistula healing". However, studies have been limited by their use of subjective outcomes and observational designs. Ultimately, further interventional, randomized controlled trials looking into the relationship between drug exposure and fistula outcomes are needed.