A diffeomorphism $f$ of a compact manifold $X$ is pseudo-isotopic to the identity if there is a diffeomorphism $F$ of $X\times I$ which restricts to $f$ on $X\times 1$, and which restricts to the identity on $X\times 0$ and $\partial X\times I$. We construct examples of diffeomorphisms of 4-manifolds which are pseudo-isotopic but not isotopic to the identity. To do so, we further understanding of which elements of the "second pseudo-isotopy obstruction", defined by Hatcher and Wagoner, can be realised by pseudo-isotopies of 4-manifolds. We also prove that all elements of the first and second pseudo-isotopy obstructions can be realised after connected sums with copies of $S^2\times S^2$.

57 pages, 18 figures. v2: Additional references added for examples of diffeomorphisms of 4-manifolds which are pseudo-isotopic to the identity. v3: Updated with comments from thesis examination. Fixed typographical errors, and clarified exposition in Sections 2.4 and 8