I want to begin by stating that most players bluff less often than most people think. If they bet, they often times have something. Perhaps they really just had some good cards. You can call them down sometimes (just to "keep them honest"), but sometimes they are just really lucky too.
With this said, there are many things that can help you "spot bluffs" more often. If a live game, then tells is a very helpful tool if found. However, in most cases (and especially for online) you can suspect a bluff when their "story doesn't add up."
For example: let us say that you are heads up. You have the button (cards are not relevant for this example).
Say it is checked to the Flop:
Kc, 2h, 2d
Both check.
Turn: 4s
Both check.
River: 8s
They bet the pot. You...?
Maybe you wouldn't have checked this way and of course you would know your cards, but this is just an example I made up. Is your opponent likely bluffing or not? This of course depends greatly on many factors: What is their play-style? How aggressive are they usually? How do they perceive you? (Table Image) and so on.
When players bet big on the river like this, they usually have it. You can probably assume that this person doesn't have pocket Aces or Pocket Kings etc. here though. Why? Well, maybe they have it if they are "trappy" by nature, but they didn't raise pre-flop, so it is less likely they have a premium hand like that. This flop is also a "hit or miss flop" that they either hit really hard or have nothing. When they check the flop and then check the Turn, they are representing weakness. Maybe they have it and maybe not, but the River bet is really polarizing.
They are either saying: I've got this hand won, or I am bluffing. If they had a hand like A4, then they would probably bet smaller to value bet or just check it down if they weren't too sure.
Therefore, the "story" doesn't "add up" for certain hands, so you can eliminate those options as likely.
In this example, it is my personal opinion that they are either bluffing or have something like three of a kind in 2, but this isn't too likely in my mind since they might have bet on the Flop or Turn with a made hand like that. They are likely bluffing in my example (also a rainbow board so Flushes are of no concern here and the lower numbers are less likely to be held - especially when they bet big at the end), but typically a big polarizing bet on the River like this means they are better.
Hope my example helps