This paper presents a historical and conceptual analysis of a group of research strategies known as the Single-Case Methods (SCMs). First, we present an overview of the SCMs, their history, and their major proponents. We will argue that the philosophical roots of SCMs can be found in the ideas of authors who recognized the importance of understanding both the generality and individuality of psychological functioning. Second, we will discuss the influence that the natural sciences' attitude toward measurement and experimentation has had on SCMs. Although this influence can be traced back to the early days of experimental psychology, during which incipient forms of SCMs appeared, SCMs reached full development during the subsequent advent of Behavior Analysis (BA). Third, we will show that despite the success of SCMs in BA and other (mainly applied) disciplines, these designs are currently not prominent in psychology. More importantly, they have been neglected as a possible alternative to one of the mainstream approaches in psychology, the Null Hypothesis Significance Testing (NHST), despite serious controversies about the limitations of this prevailing method. Our thesis throughout this section will be that SCMs should be considered as an alternative to NHST because many of the recommendations for improving the use of significance testing (Wilkinson & the TFSI, 1999) are main characteristics of SCMs. The paper finishes with a discussion of a number of the possible reasons why SCMs have been neglected.