This article brings up some of the concerns with cryptozoology (although someone failed to tell the author that practically no one takes Australia's Rex Gilroy seriously).
I wrote in response on the Science Writers LinkedIn board:
I don't think we'll find anything as far out as an ape in North America, or a plesiosaur in a lake, but a few of the "major" species of cryptozoology are ecologically possible and still might prove valid.
The article mentions the yarri or Queensland marsupial tiger: there are some impressive sightings, but they've tailed off: it may be one of the species in the genus thylacoleo lingered until very recenty.
The orang pendek, an ape of Sumatra and neighboring regions, usually reddish and habitually bipedal when on the ground, has a good sighting record and some unidentified hairs: No less an authority than Dr. John MacKinnon reported its tracks. While mostly bipedal, it's unknown whether it's more closely related to the gibbons (some of which are habitually bipedal on the ground) or the orangutans, which would require a more drastic evolutionary modification. (Speculation on a connection with the Flores hobbits is at the outer bound of possibility but would be really cool.)
None of the famous "lake monsters" seems plausible or even possible. There is, though, an interesting case in Alaska's Lake Iliamna: sturgeon have never been caught closer than the Gulf of Alaska, but good sightings, including aerial observations, indicate there may be an overlooked population with some very large individuals.
I still suspect there could be an extremely large eel or eel-like fish as the bottom of some of the "sea serpent" stories. A conger the size of an oarfish could explain some of the more puzzling sightings, most notably that by two British naturalists from the yacht Valhalla in 1905. Congers have been seen rushing about at the surface with head and forebody out of the water and lying sideways at the surface, appearing to undulate vertically: A very prominent zoologist, the late Dr. Maurice Burton, observed these activities but had no explanation for them.
Many people who call themselves cryptozoologists are terrible scientists, erecting whole species on the basis of a few reports (sometimes one) regardless of whether the proposed animal has any fossil record or makes any sense ecologically. Still, the hypothesis "there is an unclassified ape in Sumatra" is a perfectly good falsifiable (Karl Popper style) hypothesis, even though the resources to falsify it may not be available.
So no Nessie, no sasqtach... but as the discovery of a new tapir, new peccary, new beaked whale, and two new dolphins in the last few years remind us, it's still worth looking.