Sensitive biomarkers are lacking in amyotrophic lateral sclerosis (ALS). Muscle ultrasound (MUS) can quantify muscle thickness and echointensity (EI). We evaluated the rate of muscle atrophy in ALS using MUS. Ten patients had serial unilateral MUS examination of biceps, wrist flexors, and tibialis anterior over 6 months. The rates of change of muscle thickness and EI were determined. Muscle thickness declined at a mean rate of -0.663 mm/month (P = 0.0014), greatest in biceps. Muscle thickness correlated moderately with ALSFRS-R, grip dynamometry, and body weight. There was no change in EI. MUS can quantify the rate of reduction in muscle thickness in ALS patients. The lack of strong correlation between muscle thickness and standard ALS measures may reflect limited sensitivity in these conventional measures. The rate of change of muscle thickness merits further study as a potential biomarker in ALS, particularly when considering biceps brachii as a candidate.