A quarter of century ago, Farwell and Donchin (1988) described their mental prosthesis for “talking off the top of your head.” This innovative communication system, later named P3-speller, has been the most investigated and tested brain–computer interface (BCI) system, to date. A main goal of the research on P3-spellers was the development of an effective assistive device for patients with severe motor diseases. Among these patients are those affected by amyotrophic lateral sclerosis (ALS). ALS patients have become a target population in P3-speller (and more generally in BCI) research. The P3-speller relies on the visual sensory modality, and it can be controlled by requiring users to actively move their eyes. Unfortunately, eye-movement control is usually not spared in the last stages of ALS, and, then, it is definitively lost in the case of complete paralysis. We reviewed the literature on ALS patients tested by means of P3-speller systems. Our aim was to investigate the evidence available to date of the P3-spellers effectiveness in ALS patients. To address this goal, a meta-analytic approach was adopted. The pooled classification accuracy performance, among retrieved studies, was about 74%. This estimation, however, was affected by significant heterogeneity and inconsistency among studies. This fact makes this percentage estimation (i.e., 74%) unreliable. Nowadays, the conclusion is that the initial hopes posed on P3-speller for ALS patients have not been met yet. In addition, no trials in which the P3-speller has been compared to current assistive technologies for communication (e.g., eye-trackers) are available. In conclusion, further studies are required to obtain a reliable index of P3-speller effectiveness in ALS. Furthermore, comparisons of P3-speller systems with the available assistive technologies are needed to assess the P3-speller usefulness with non-completely paralyzed ALS-patients.