First, let me explain the movie title.
The firehouse featured in the movie has 2 vehicles. One of them is the more conventional fire truck you see around, the one with the water hoses. That truck is codenamed Engine 33 in this movie. Ladder 49 is its companion truck, the one with the mega-ladder. This truck comprises of the brave men in the fire department's rescue team, those who risk their lives going into burning buildings without water (unlike Engine 33's), for the sole mission of saving other people's lives.
Which raises the question everyone asks of emergency responders (police, fire dept, etc) - what makes them do what they do? In this case, also raised in the movie, what makes them rush into a burning building when everyone else is running out?
We follow the life of Joaquin Phoenix's character, Jack Morrison, whom we see from rookie firefighter (waterboy) to hero, from singlehood to fatherhood. This film, through his character, humanizes emergency responders, their lives, their camaraderie, their courage. It also explores relationships within their families, which is key, as family members struggle to understand the risks their spouses/fathers undertake everyday in their job.
Don't expect another Backdraft, which was more of an "arson-whodunnit", with spectacular beastly fires engulfing the screen. This film dwells more on characterization and drama, with well placed action set pieces between slow moments which will set you thinking, and at the end of the film, appreciating the courage of these brave men and the threats they face daily in their job.