Trimethylamine (TMA) is a volatile, foul-smelling, diet-derived amine, primarily generated in the colon and metabolized in the liver to its odorless N-oxide (TMAO). In primary trimethylaminuria (TMAU), an inherited deficiency in flavin-containing monooxygenase 3 leads to elevated systemic TMA levels. The excretion of elevated amounts of TMA in sweat, breath, urine and other bodily secretions gives individuals affected by TMAU a smell resembling that of rotten fish. Although the disorder might not seem an important health problem, its social and psychological burden can be devastating. To date, no treatment modifying the disorder exists and only a few pharmacological therapies provide modest and transient benefits. This review provides an overview of investigated TMAU treatments and outlines promising new research directions.