Abstract The high point of the falsification of physical theories in a standard view of the philosophy of science is the so-called crucial experiment. This experiment is a kind of manipulated empirical test, which provides the criterion for distinguishing between two rival hypotheses, where one is an acceptable theory due to passing the test, and the other turns out to be an unacceptable theory as it does not pass the test. The crucial experiment was supposed to play a significant role because, in virtue of an empirical disconfirmation of one theory, the experiment was assumed to confirm the other as true. However, in 1906, in La théorie physique, son object et la structure (hereafter quoted in English translation as The Aim and Structure of Physical Theory (1906/1954)), Pierre Duhem famously argued against this view and stated that crucial experiments in physics are impossible as they are necessarily ambiguous and logically incomplete. His contention rested on the claim that, “[a] physical theory is not an explanation [of true reality in itself in virtue of some broad metaphysical ramification of physics]. It is a system of mathematical propositions, deduced from a small number of principles, which aim to represent as simply, as completely, and as accurately as possible a set of experimental laws” (ibid., p. 19). Furthermore, different theories could be equally suitable to represent a given group of experimental laws. And, assuming holism, no hypothesis could be tested in isolation, but merely as a part of a set of an entire scientific theory. The problem which Duhem identified in 1906 was slightly overshadowed and neglected in mainstream philosophy of science until the appearance of a challenging paper by Willard Van Orman Quine published in 1951 and entitled “Two Dogmas of Empiricism”. Quine’s paper caused a revival of interest in Duhem’s original formulation and gave a new impulse towards the problem in the form of the so-called Duhem-Quine thesis. The aim of this paper is to reconsider whether Duhem was right to argue that there are no crucial experiments in physics. In order to assess the validity of the thesis, first, this paper makes an exposition of Duhem’s arguments in their favour, and analyses the major criticisms of this position offered in the subject-literature of Adolf Grünbaum, who explicitly attacked the arguments for the thesis as inconclusive and false. Then, this paper presents possible modes of defence of the Duhem-Quine thesis and argues that the original formulation of the thesis is well qualified and plausible. Finally, this paper offers a pragmatic interpretation of the theory choice.