Desmoid tumors (DTs) are rare, locally infiltrating tumors that do not metastasize. The lack of a standard treatment approach makes choosing the most appropriate treatment challenging. Asymptomatic patients are often managed with watchful observation, as spontaneous regression occurs in up to 20% of cases. Surgical resection is no longer favored due to high morbidity and relapse rates. Systemic therapy has evolved over the decades, with chemotherapy, hormonal therapy, and non-steroidal anti-inflammatory drugs (NSAIDs) being used in the past. Tyrosine kinase inhibitors (TKIs) have gained prominence in recent years, and gamma-secretase inhibitors (GSIs) have shown significant clinical benefits, particularly nirogacestat, which has been approved by the USFDA. Several Wnt pathway inhibitors are also under development. Cryoablation, a minimally invasive technique, has shown clinical benefit in patients with extra-abdominal DTs. The recent approval of nirogacestat marks a new era in the treatment of DTs, with several new molecules expected to be approved in the coming years.Desmoid tumors (DTs) are rare, locally infiltrating tumors that do not metastasize. The lack of a standard treatment approach makes choosing the most appropriate treatment challenging. Asymptomatic patients are often managed with watchful observation, as spontaneous regression occurs in up to 20% of cases. Surgical resection is no longer favored due to high morbidity and relapse rates. Systemic therapy has evolved over the decades, with chemotherapy, hormonal therapy, and non-steroidal anti-inflammatory drugs (NSAIDs) being used in the past. Tyrosine kinase inhibitors (TKIs) have gained prominence in recent years, and gamma-secretase inhibitors (GSIs) have shown significant clinical benefits, particularly nirogacestat, which has been approved by the USFDA. Several Wnt pathway inhibitors are also under development. Cryoablation, a minimally invasive technique, has shown clinical benefit in patients with extra-abdominal DTs. The recent approval of nirogacestat marks a new era in the treatment of DTs, with several new molecules expected to be approved in the coming years.