We present a case of stiff person syndrome (SPS) with a description of the diagnostic challenges and a discussion of the implication of novel antibodies. SPS is a rare neurological disorder presenting with severe rigidity, muscle spasms and impaired gait function, and diagnosis is often delayed due to low awareness. SPS is classically associated with antibodies directed against glutamic acid decarboxylase or amphiphysin. However, recent advances have contributed to our understanding because of detection of several new antibodies, which cause SPS, mostly with additional neurological/systemic manifestations.