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Guidelines for primary care clinicians on monitoring and safety guidelines regarding Janus kinase and tyrosine kinase 2 inhibitors in the treatment of inflammatory skin conditions are often unclear. This review aims to provide the primary care physician with a review of clinically relevant and updated information regarding the monitoring and overall profile of these medications. To do so, a systematic review was conducted using the PubMed database and relevant Food and Drug Administration (FDA) approved drug inserts from manufacturers. Janus kinase and tyrosine kinase 2 inhibitors have recently gained FDA approval for the treatment of several inflammatory skin conditions including atopic dermatitis, plaque psoriasis, alopecia areata, and vitiligo. There is a known box warning associated with the Janus kinase inhibitors that create the need for monitoring and close follow-up while patients are undergoing these treatments. Although these medications are often prescribed by specialists, as their use becomes more prevalent and therapies continue to gain approval for the treatment of these commonly encountered conditions, it is important for the primary physician to be updated and aware of the current monitoring guidelines and safety profile for this class of medication. Both Janus kinase inhibitors and tyrosine kinase 2 inhibitors display significant efficacy in the treatment of their approved conditions and research continues to move forward with the approval of more medications from these classes.