As of Mirth Connect 2.1, there is only one required upgrade guide. Mirth Connect 2.1+ upgrading requires little to no user intervention, depending on your configuration, and skipping versions while upgrading requires no additional instruction.
If you are upgrading from a version older than Mirth Connect 2.1, each Mirth Connect release has an associated upgrade guide that is listed in the tree to the left. If you are upgrading to a new version and would like to skip a version that was released in the interim (i.e. 1.8 to 2.1), then you should read both upgrade guides, make note of changes between each version, and follow the upgrade guide that applies to your original version. Some instructions in the original version's upgrade guide may be outdated for the version you are upgrading to.