In dealing with a disease like amyotrophic lateral sclerosis (ALS) that has no fully known cause and no cure, clinical trials are becoming the sole vehicle of hope to identify effective treatments. The World Federation of Neurology Committee of Motor Neuron Disease has published revised diagnostic criteria for ALS and guidelines on the design and conduct of clinical trials in ALS. These criteria and guidelines are helpful since we have no diagnostic or surrogate markers in ALS. Given this, clinical trialists must rely on currently available measurement techniques, including survival rate, neuromuscular assessments, clinimetrics, and quality of life (QoL). Survival has been used in several clinical trials, such as riluzole, SR57746A, and new brain-derived neurotrophic factor (BDNF) trials, but this has inherent problems. Tufts quantitative neuromuscular evaluation (TQNE), including the maximal voluntary isometric muscle contraction (MVIC), expresses a direct clinical feature of ALS; however, it has not been able to demonstrate positive results in trials, such as ciliary neurotrophic factor (CNTF), BDNF, and gabapentin. The use of TQNE remains important, though in investigator-driven trials. Among all measurement techniques, forced or slow vital capacity and ALS functional rating scale (ALSFRS) appear the most universally accepted evaluation techniques in ALS trials. For QoL measurements, only generic QoL instruments have been available until recently. Now ALS-specific QoL tools, such as the ALS assessment questionnaire-40 (ALSAQ-40), have just been introduced.